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Neurodevelopmental risk copy number variants in adults with intellectual disabilities and comorbid psychiatric disorders

  • Johan H. Thygesen (a1), Kate Wolfe (a1), Andrew McQuillin (a1), Marina Viñas-Jornet (a2), Neus Baena (a2), Nathalie Brison (a3), Greet D'Haenens (a4), Susanna Esteba-Castillo (a5), Elisabeth Gabau (a2), Núria Ribas-Vidal (a5), Anna Ruiz (a2), Joris Vermeesch (a6), Eddy Weyts (a4), Ramon Novell (a5), Griet Van Buggenhout (a7), André Strydom (a8), Nick Bass (a1), Miriam Guitart (a2) and Annick Vogels (a9)...

Abstract

Background

Copy number variants (CNVs) are established risk factors for neurodevelopmental disorders. To date the study of CNVs in psychiatric illness has focused on single disorder populations. The role of CNVs in individuals with intellectual disabilities and psychiatric comorbidities are less well characterised.

Aims

To determine the type and frequency of CNVs in adults with intellectual disabilities and comorbid psychiatric disorders.

Method

A chromosomal microarray analysis of 599 adults recruited from intellectual disabilities psychiatry services at three European sites.

Results

The yield of pathogenic CNVs was high – 13%. Focusing on established neurodevelopmental disorder risk loci we find a significantly higher frequency in individuals with intellectual disabilities and comorbid psychiatric disorder (10%) compared with healthy controls (1.2%, P<0.0001), schizophrenia (3.1%, P<0.0001) and intellectual disability/autism spectrum disorder (6.5%, P < 0.00084) populations.

Conclusions

In the largest sample of adults with intellectual disabilities and comorbid psychiatric disorders to date, we find a high rate of pathogenic CNVs. This has clinical implications for the use of genetic investigations in intellectual disability psychiatry.

Declaration of interest

None.

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Copyright

This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.

Corresponding author

Correspondence: Annick Vogels, Department of Human Genetics, Centre for Human Genetics, University Hospitals Leuven, O&N I Herestraat 49 - Box 602, KU Leuven, 3000 Leuven, Belgium. Email: annick.vogels@uzleuven.be

Footnotes

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This work has not been presented previously, but a subset of data from 202 samples included here has previously been presented in Wolfe et al (2016), four cases in Vogels et al (2014) and one case in each of Vanmarsenille et al (2014), Denayer et al (2012) and Hannes et al (2009); see Supplementary File 1 (available at https://doi.org/10.1192/bjp.2017.65) for the full references for these papers.

**

These authors contributed equally to the work as first authors.

***

These authors contributed equally to the work as last authors.

Footnotes

References

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Neurodevelopmental risk copy number variants in adults with intellectual disabilities and comorbid psychiatric disorders

  • Johan H. Thygesen (a1), Kate Wolfe (a1), Andrew McQuillin (a1), Marina Viñas-Jornet (a2), Neus Baena (a2), Nathalie Brison (a3), Greet D'Haenens (a4), Susanna Esteba-Castillo (a5), Elisabeth Gabau (a2), Núria Ribas-Vidal (a5), Anna Ruiz (a2), Joris Vermeesch (a6), Eddy Weyts (a4), Ramon Novell (a5), Griet Van Buggenhout (a7), André Strydom (a8), Nick Bass (a1), Miriam Guitart (a2) and Annick Vogels (a9)...

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Neurodevelopmental risk copy number variants in adults with intellectual disabilities and comorbid psychiatric disorders

  • Johan H. Thygesen (a1), Kate Wolfe (a1), Andrew McQuillin (a1), Marina Viñas-Jornet (a2), Neus Baena (a2), Nathalie Brison (a3), Greet D'Haenens (a4), Susanna Esteba-Castillo (a5), Elisabeth Gabau (a2), Núria Ribas-Vidal (a5), Anna Ruiz (a2), Joris Vermeesch (a6), Eddy Weyts (a4), Ramon Novell (a5), Griet Van Buggenhout (a7), André Strydom (a8), Nick Bass (a1), Miriam Guitart (a2) and Annick Vogels (a9)...
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